Migraine headache is a chronic and disabling condition affecting a significant portion of the population throughout the world. The pharmacologic management of migraine has traditionally focused on two approaches: symptomatic or acute treatment and prophylactic therapy. The objective of acute treatment is to reduce the intensity and duration of pain with its attendant symptoms and to optimize the patient's ability to function normally whereas the major objective of prophylactic therapy is the reduction of frequency, duration, and intensity of attacks.
A variety of treatment strategies are available for the prophylactic treatment of migraines including beta-blocking drugs (e.g., propranolol), amitriptyline, flunarizine, serotonin antagonists (e.g., methysergide) and nonsteroidal anti-inflammatory drugs (e.g., naproxen) are the major classes of agents that have been used in the prophylactic treatment of migraines. See e.g., Deleu et al (1998) Clin. Neuropharmacol. 21:267–79 for review. Strategies for the acute treatment of migraines are also known which generally involve the use of simple analgesics, nonsteroidal anti-inflammatory drugs, antiemetics, narcotic analgesics, ergot derivatives, or serotonin-agonists, either alone or in combination. For example, dihydroergotamine (DHE) has been used for several decades for treatment of acute migraine headache and produces good relief in 70–80% of subjects at 2 hours after administration (Callaham and Raskin (1986) Headache 26;168–171). Sumatriptan produces similar efficacy, as do several newer serotonin 1B/1D receptor agonists (Cady et al. (1991) JAMA 265:2831–2835; Mathew et al. (1992) Arch Neurol. 49:1271–1276 and Rapoport (1997) Cephalalgia 17: 464–465).
However, a significant portion of migraine patients remain who either require narcotic analgesic treatment or who may have significant disability despite the use of non-narcotic analgesia. A large number of patients go to hospital emergency rooms for acute treatment of prolonged migraine headache (Klapper et al. (1991) 31:523–524). Many of those patients may have used an ergotamine or triptan so that use of DHE, injectable sumatriptan or other related compounds would be contraindicated. Also, cardiovascular risk factors limit the safety of triptan use or dihydroergotamine; the new DHE nasal spray (Migranal) carries the same warnings as the triptans. (Kelly (1995) Neurology 45:11–13; Maxalt:MSD, Ltd. (1998) Insert; and Physician's Desk Reference, 53 Edition, Medical Economics Comp. (1999) pp 2061). Finally, a number of patients presenting to the emergency room have associated analgesic rebound headache, with or without chronic daily headache, in which cases further analgesic use is problematic (Silberstein and Young (1995) Drug Saf. 13:133–144).